N-[3-(5-Oxo-10,11-dihydro-5H-dibenzo[a,d]cyclo­hepten-2-ylamino)phen­yl]furan-3-carboxamide

Angelika Dorn; Dieter Schollmeyer; Stefan A Laufer

doi:10.1107/S1600536810013450

. 2010 Apr 17;66(Pt 5):o1100. doi: 10.1107/S1600536810013450

N-[3-(5-Oxo-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-2-ylamino)phenyl]furan-3-carboxamide

Angelika Dorn ^a, Dieter Schollmeyer ^b, Stefan A Laufer ^a,^*

PMCID: PMC2979018 PMID: 21579152

Abstract

In the title compound, C₂₆H₂₀N₂O₃, the two aromatic rings of the tricyclic unit are oriented at a dihedral angle of 54.53 (9)°. The crystal structure displays intermolecular N—H⋯O hydrogen bonding.

Related literature

For palladium-catalyzed amination reactions of aryl halides with anilines, see: Jensen et al. (2004 ▶); Grasa et al. (2001 ▶). For p38 inhibitors based on dibenzosuberones, see: Laufer et al. (2006 ▶).

Experimental

Crystal data

C₂₆H₂₀N₂O₃
M _r = 408.44
Monoclinic,
a = 10.7691 (7) Å
b = 21.746 (1) Å
c = 8.8666 (6) Å
β = 101.934 (2)°
V = 2031.6 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 173 K
0.30 × 0.20 × 0.10 mm

Data collection

Bruker SMART APEXII diffractometer
22214 measured reflections
4856 independent reflections
3347 reflections with I > 2σ(I)
R _int = 0.044

Refinement

R[F ² > 2σ(F ²)] = 0.050
wR(F ²) = 0.115
S = 0.99
4856 reflections
280 parameters
H-atom parameters constrained
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.30 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: PLATON.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810013450/im2187sup1.cif

e-66-o1100-sup1.cif^{(22.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810013450/im2187Isup2.hkl

e-66-o1100-Isup2.hkl^{(237.9KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N17—H17⋯O16ⁱ	0.87	2.14	2.900 (2)	146
N24—H24⋯O26ⁱⁱ	0.91	2.00	2.839 (2)	153

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Symmetry codes: (i) Inline graphic ; (ii) .

supplementary crystallographic information

Comment

p38 mitogen activated protein (MAP) kinase is a key enzyme in inflammatory diseases as it is involved in the biosynthesis of proinflammatory cytokines such as TNF-α and IL-1β (Laufer et al. 2006). Small molecule p38 inhibitors suppress the production of these cytokines and therefore p38 is an attractive and promising drug target for novel anti-inflammatory therapeutics (Laufer et al. 2006). Recently, we designed and synthesized a series of p38 inhibitors based on dibenzosuberones (Laufer et al. 2006). The title compound was prepared in the course of our studies on dibenzo[a,d]cycloheptan-5-ones as potent p38 MAP kinase inhibitors.

The structure of the title compound, at 173 (2) K has monoclinic (P2₁/c) symmetry. In the molecule (Fig.1), rings A (C1—C4, C14, C15) and B (C6—C11) are, of course, planar and they are oriented at a dihedral angle of A/B = 54.53 (9)°. The intramolecular C21—H21···O26 (2.66 Å) interaction stabilizes the conformation of the molecule. In the crystal structure the hydrogen bonds N17—H17···O16 (2.90 Å) and N24—H24···O26 (2.84 Å) link the molecule into double layers.

Experimental

For the preparation of the title compound a mixture of 500 mg (2.1 mmol) 2-chloro-10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-one, 420 mg (2.1 mmol) N-(3-aminophenyl)-3-furamide, 940 mg (8.4 mmol) KOtert-Bu, 90 mg (0.19 mmol) 2-(dicyclohexylphosphino)-2'-, 4'-, 6'-triisopropylbiphenyl and 20 mg (0.09 mmol) Pd(OAc)₂ in 3 ml absolute tert-butanol and 7 ml absolute toluol was stirred for 4 h at 363 K under an atmosphere of argon. The mixture was diluted with water and then extracted with ethyl acetate. The extracts were combined, washed with saturated saline solution, dried over Na₂SO₄ and then evaporated under reduced pressure. The residue was purified by flash chromatography (SiO₂ 60, n-hexane / ethyl acetate 3 + 2) (yield: 17.2 %). Crystals of the title compound were obtained by slow evaporation of a methanol / diethyl ether solution at room temperature.